Caracterização das principais mutações de ponto do DNA mitocondrial em um grupo de pacientes com doenças neurodegenerativas

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

Mitochondrial disease are genetic and clinic heterogeneous entities that are variable in age of onset, clinical severity and evolution. They are classified in abnormalities of nuclear DNA or mitochondrial DNA (mtDNA). Point mutations are found in mitochondrial genomes and most frequent phenotypes are MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes), MERRF (myoclonic epilepsy and ragged-red fibers), NARP (neuropathy, ataxia, and retinitis pigmentosa), MILS (maternally inherited Leigh syndrome) e LHON (Leber Hereditary Optic Neuropathy). The objectives ofthis study were: a) To search for the presence of the most frequently described point mutations in the mtDNA in patients with clinical features suggesting MELAS, MERRF, NARP, MILS or LHON. b) To study the relationship between genotype and phenotype in patients with mutation. c) Quantify the heteroplasmy in atIected individuals. Mitochondrial DNA was isolated &om peripheralleukocytes and was purified by use of the phenol clorophormio method. PCR was used to amplify the critical regions. Restriction-fragment analysis was used to screen for mtDNA point mutations, that was confinned by DNA sequencing. The percentage of mutant mtDNA was determined by the system Kodak EDAS 290. We screened 120 patients for seven points ofmutation responsible for MELAS, MERRF, NARP, MILS and LHON and we identified seven patients with a mtDNA point mutation. Eight patients were suspected of Leber disease, in two of them, we found the G11778 mutation, and another patient presented the G3460A mutation. One patient with the clinical diagnosis of MELAS, as well as his mother and three asymptomatic sisters, showed the A3243G mutation. One patient had the A8344G mutation responsible for MERRF and two brothers with NARP features had the G11778A mutation that was associated with Leber disease. No mutation at 8993 nucleotide was observed

ASSUNTO(S)

doenças neuromusculares doenças neurodegenerativas encefalomiopatias mitocondriais

ACESSO AO ARTIGO

Documentos Relacionados